The frequencies of HLA-DR and DQ antigens in 24 Chinese patients with Behçet's disease (BD) were ... more The frequencies of HLA-DR and DQ antigens in 24 Chinese patients with Behçet's disease (BD) were calculated and compared with those in 130 healthy control Chinese and those in 80 Chinese patients with recurrent oral ulcers (ROU). Although an increased trend of DRw6 and DRw8 antigens in patients with BD was noted, there was no significant difference in frequencies of HLA-DR and DQ antigens between patients with BD and healthy control subjects or patients with ROU after correction of P values (Pc>0.05). Further analysis of our data of the phenotype frequencies of DRw6 and DRw8 antigens according to the subtypes of BD also showed the increased frequencies of DRw6 and DRw8 antigens in patients with mucocutaneous type of BD as compared with those in healthy control subjects. However, only the phenotype frequency of DRw8 antigen in patients with mucocutaneous type of BD was significantly higher than that in patients with ROU (P< 0.005, PC < 0.05, relative risk= 17.7, and etiologic fraction =0.30). This significant increase of the phenotype frequency suggests that the gene coding for HLA-DRw8 antigen in patients with ROU was only partially (30%) responsible for susceptibility to the mucocutaneous type of BD.
Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an... more Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer.Methods: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed.Results: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 ± 7 months. The mean time for malignant transformation was 22 ± 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy.Conclusions: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.
Background: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor nec... more Background: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor necrosis factor (TNF)-α is an important inflammatory mediator and a critical cytokine for adequate host defense. Our previous studies have shown that 14–43% and 59–63% of patients in the ulcerative stage of major, minor or herpetiform RAU have significantly higher than normal serum levels of interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU patients in the ulcerative stage had a significantly higher than normal serum level of TNF-α and assessed whether treatment with levamisole can modulate serum TNF-α levels in RAU patients.Methods: This study used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of TNF-α in 146 patients with RAU, nine patients with traumatic ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum TNF-α levels higher than 5.0 pg/ml were treated with levamisole for 0.5–4 months and their serum TNF-α levels were measured after treatment.Results: We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type, 20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had a serum level of TNF-α greater than the upper normal limit of 7.4 pg/ml. The mean serum level of TNF-α in patients with RAU (9.1 ± 1.0 pg/ml, P < 0.001), major type RAU (11.6 ± 1.9 pg/ml, P < 0.001), minor type RAU (6.9 ± 0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 ± 2.7 pg/ml, P < 0.001) was higher than that (3.8 ± 0.2 pg/ml) in normal control subjects. The mean serum TNF-α level was significantly higher in patients with major type RAU than in patients with minor type RAU (P < 0.05) and was significantly higher in major type RAU patients in the exacerbation stage than in the post-exacerbation stage (P < 0.05). In 55 RAU patients with serum TNF-α levels higher than 5.0 pg/ml, treatment with levamisole for a period of 0.5–4 months could significantly reduce the serum TNF-α level from 16.4 ± 1.9 to 5.8 ± 0.6 pg/ml (P < 0.001).Conclusions: We conclude that a significantly higher than normal serum level of TNF-α can be detected in 20–39% of patients in the ulcerative stage of major, minor or herpetiform RAU. The serum TNF-α level may be associated with the severity and the stage of RAU. Levamisole can modulate serum TNF-α levels in RAU patients.
Background: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas wi... more Background: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three.Methods: This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers.Results: Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 ± 43%) was significantly lower than that of HMB-45 (83 ± 28%, P = 0.0065) or of S-100 (79 ± 33%, P = 0.0237).Conclusions: Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.
Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-s... more Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-standing symptomatology, but the fact that the lesions are indeed malignant has been proven by the repeated demonstration that they can metastasize to distant organs. Suitable prognostic factors are lacking and therapeutic strategy still remains controversial. Expression of human telomerase reverse transcriptase (hTERT) is associated with most human malignancies and high levels have been correlated with poor prognosis in many cancers. In comparison, overexpression of cyclin-D1 occurs in several malignancies and has been associated with aggressive tumor behavior and poorer prognosis. In this study, we collected 16 olfactory neuroblastomas from the Kaohsiung Medical University Hospital. The aim was to investigate the value of immunoexpression of hTERT and cyclin-D1 in correlation with clinicopathologic features of olfactory neuroblastoma. Low and high cyclin-D1 expression was found in 6 and 10 cases, respectively. For hTERT, low and high protein expression was detected in 5 and 11 tumors, respectively. Cyclin-D1 expression was not correlated with selected parameters. However, high hTERT expression was significantly correlated with high Kadish stage. In conclusion, high hTERT expression can be considered a potential indicator of aggressive olfactory neuroblastoma.
Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL... more Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.Methods: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5–5.5 months and their serum IL-6 levels were measured after treatment.Results: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 ± 3.1 pg/ml, P < 0.001), EOLP (3.4 ± 3.2 pg/ml, P < 0.001), major type EOLP (4.9 ± 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 ± 3.0 pg/ml, P < 0.01), or NEOLP (4.2 ± 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 ± 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 ± 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 ± 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only.Conclusion: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.
Abstract: The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in... more Abstract: The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behçet’s disease (BD) were calculated and compared with those in 310 healthy control Chinese and with those in 80 Chinese patients with recurrent aphthous stomatitis (RAS). We found that the phenotype frequency of HLA-DRw8 [corrected P (Pc)<0.005] and the haplotype frequencies of HLA-DRw8/DQw1 (Pc<0.005), -DRw8/DQw5(w1) (Pc<0.0005), -DRw12(5)/DQw1 (Pc<0.005), -DRw12(5)/DQw6(w1) (Pc< 0.0005), and -DRw52/DQw1 (Pc<0.005) in patients with the MC type of BD were significantly greater than those in healthy control subjects. This finding suggests that individual Chinese with HLA-DRw8 antigen and HLA-DRw8/DQw1, -DRw8/DQw5(w1), -DRw12(5)/DQw1, -DRw12(5)/DQw6(w1) and -DRw52/DQw1 haplotypes are more likely to have the MC type of BD. Furthermore, the relative risks (RRs) of HLA–DRw8/DQw1 (5.6), -DRw8/DQw5 (w1) (10.0), and -DRw12(5)/DQw6(w1) (14.4) haplotypes in patients with the MC type of BD were equal to or higher than the RR of HLA-DRw8 phenotype (5.6), suggesting that some of the HLA-DR/DQ haplotypes may play more important roles than the individual HLA-DR and -DQ phenotypes for the development of the MC type of BD. The phenotype frequencies of HLA-DR5 (Pc<0.01), -DRw8 (Pc<0.005) and -DQw1 (Pc<0.05) as well as the haplotype frequencies of HLA-DR5/DQw1 (Pc<0.005) and -DRw8/DQw1 (Pc<0.00005) in patients with the MC type of BD were significantly higher than those in patients with RAS. Moreover, the RRs of HLA-DR5/DQw1 (29.1) and -DRw8/DQw1 (47.4) haplotypes were greater than the RRs of HLA-DR5 (10.4), -DRw8 (23.4) and -DQw1 (4.0) antigens. These results suggest that some specific HLA-DR/DQ haplotypes may be more important than the individual HLA-DR and -DQ phenotypes in the disease shift from RAS to the MC type of BD.
The frequencies of HLA-DR and DQ antigens in 24 Chinese patients with Behçet's disease (BD) were ... more The frequencies of HLA-DR and DQ antigens in 24 Chinese patients with Behçet's disease (BD) were calculated and compared with those in 130 healthy control Chinese and those in 80 Chinese patients with recurrent oral ulcers (ROU). Although an increased trend of DRw6 and DRw8 antigens in patients with BD was noted, there was no significant difference in frequencies of HLA-DR and DQ antigens between patients with BD and healthy control subjects or patients with ROU after correction of P values (Pc>0.05). Further analysis of our data of the phenotype frequencies of DRw6 and DRw8 antigens according to the subtypes of BD also showed the increased frequencies of DRw6 and DRw8 antigens in patients with mucocutaneous type of BD as compared with those in healthy control subjects. However, only the phenotype frequency of DRw8 antigen in patients with mucocutaneous type of BD was significantly higher than that in patients with ROU (P< 0.005, PC < 0.05, relative risk= 17.7, and etiologic fraction =0.30). This significant increase of the phenotype frequency suggests that the gene coding for HLA-DRw8 antigen in patients with ROU was only partially (30%) responsible for susceptibility to the mucocutaneous type of BD.
Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an... more Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer.Methods: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed.Results: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 ± 7 months. The mean time for malignant transformation was 22 ± 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy.Conclusions: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.
Background: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor nec... more Background: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Tumor necrosis factor (TNF)-α is an important inflammatory mediator and a critical cytokine for adequate host defense. Our previous studies have shown that 14–43% and 59–63% of patients in the ulcerative stage of major, minor or herpetiform RAU have significantly higher than normal serum levels of interleukin (IL)-6 and IL-8, respectively. In this study, we examined whether RAU patients in the ulcerative stage had a significantly higher than normal serum level of TNF-α and assessed whether treatment with levamisole can modulate serum TNF-α levels in RAU patients.Methods: This study used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of TNF-α in 146 patients with RAU, nine patients with traumatic ulcers (TU), and 54 normal control subjects. Fifty-five RAU patients with serum TNF-α levels higher than 5.0 pg/ml were treated with levamisole for 0.5–4 months and their serum TNF-α levels were measured after treatment.Results: We found that 29% (42 of 146) RAU patients as well as 39% (24 of 61) major type, 20% (14 of 69) minor type, and 25% (four of 16) herpetiform type RAU patients had a serum level of TNF-α greater than the upper normal limit of 7.4 pg/ml. The mean serum level of TNF-α in patients with RAU (9.1 ± 1.0 pg/ml, P < 0.001), major type RAU (11.6 ± 1.9 pg/ml, P < 0.001), minor type RAU (6.9 ± 0.9 pg/ml, P < 0.005), or herpetiform type RAU (9.6 ± 2.7 pg/ml, P < 0.001) was higher than that (3.8 ± 0.2 pg/ml) in normal control subjects. The mean serum TNF-α level was significantly higher in patients with major type RAU than in patients with minor type RAU (P < 0.05) and was significantly higher in major type RAU patients in the exacerbation stage than in the post-exacerbation stage (P < 0.05). In 55 RAU patients with serum TNF-α levels higher than 5.0 pg/ml, treatment with levamisole for a period of 0.5–4 months could significantly reduce the serum TNF-α level from 16.4 ± 1.9 to 5.8 ± 0.6 pg/ml (P < 0.001).Conclusions: We conclude that a significantly higher than normal serum level of TNF-α can be detected in 20–39% of patients in the ulcerative stage of major, minor or herpetiform RAU. The serum TNF-α level may be associated with the severity and the stage of RAU. Levamisole can modulate serum TNF-α levels in RAU patients.
Background: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas wi... more Background: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three.Methods: This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers.Results: Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 ± 43%) was significantly lower than that of HMB-45 (83 ± 28%, P = 0.0065) or of S-100 (79 ± 33%, P = 0.0237).Conclusions: Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.
Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-s... more Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are indolent with long-standing symptomatology, but the fact that the lesions are indeed malignant has been proven by the repeated demonstration that they can metastasize to distant organs. Suitable prognostic factors are lacking and therapeutic strategy still remains controversial. Expression of human telomerase reverse transcriptase (hTERT) is associated with most human malignancies and high levels have been correlated with poor prognosis in many cancers. In comparison, overexpression of cyclin-D1 occurs in several malignancies and has been associated with aggressive tumor behavior and poorer prognosis. In this study, we collected 16 olfactory neuroblastomas from the Kaohsiung Medical University Hospital. The aim was to investigate the value of immunoexpression of hTERT and cyclin-D1 in correlation with clinicopathologic features of olfactory neuroblastoma. Low and high cyclin-D1 expression was found in 6 and 10 cases, respectively. For hTERT, low and high protein expression was detected in 5 and 11 tumors, respectively. Cyclin-D1 expression was not correlated with selected parameters. However, high hTERT expression was significantly correlated with high Kadish stage. In conclusion, high hTERT expression can be considered a potential indicator of aggressive olfactory neuroblastoma.
Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL... more Background: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.Methods: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5–5.5 months and their serum IL-6 levels were measured after treatment.Results: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 ± 3.1 pg/ml, P < 0.001), EOLP (3.4 ± 3.2 pg/ml, P < 0.001), major type EOLP (4.9 ± 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 ± 3.0 pg/ml, P < 0.01), or NEOLP (4.2 ± 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 ± 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 ± 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 ± 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only.Conclusion: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.
Abstract: The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in... more Abstract: The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behçet’s disease (BD) were calculated and compared with those in 310 healthy control Chinese and with those in 80 Chinese patients with recurrent aphthous stomatitis (RAS). We found that the phenotype frequency of HLA-DRw8 [corrected P (Pc)<0.005] and the haplotype frequencies of HLA-DRw8/DQw1 (Pc<0.005), -DRw8/DQw5(w1) (Pc<0.0005), -DRw12(5)/DQw1 (Pc<0.005), -DRw12(5)/DQw6(w1) (Pc< 0.0005), and -DRw52/DQw1 (Pc<0.005) in patients with the MC type of BD were significantly greater than those in healthy control subjects. This finding suggests that individual Chinese with HLA-DRw8 antigen and HLA-DRw8/DQw1, -DRw8/DQw5(w1), -DRw12(5)/DQw1, -DRw12(5)/DQw6(w1) and -DRw52/DQw1 haplotypes are more likely to have the MC type of BD. Furthermore, the relative risks (RRs) of HLA–DRw8/DQw1 (5.6), -DRw8/DQw5 (w1) (10.0), and -DRw12(5)/DQw6(w1) (14.4) haplotypes in patients with the MC type of BD were equal to or higher than the RR of HLA-DRw8 phenotype (5.6), suggesting that some of the HLA-DR/DQ haplotypes may play more important roles than the individual HLA-DR and -DQ phenotypes for the development of the MC type of BD. The phenotype frequencies of HLA-DR5 (Pc<0.01), -DRw8 (Pc<0.005) and -DQw1 (Pc<0.05) as well as the haplotype frequencies of HLA-DR5/DQw1 (Pc<0.005) and -DRw8/DQw1 (Pc<0.00005) in patients with the MC type of BD were significantly higher than those in patients with RAS. Moreover, the RRs of HLA-DR5/DQw1 (29.1) and -DRw8/DQw1 (47.4) haplotypes were greater than the RRs of HLA-DR5 (10.4), -DRw8 (23.4) and -DQw1 (4.0) antigens. These results suggest that some specific HLA-DR/DQ haplotypes may be more important than the individual HLA-DR and -DQ phenotypes in the disease shift from RAS to the MC type of BD.
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